The long-term objective of this research is to establish quantitative criteria for evaluating the potential effectiveness of altered fractionation schedules in radiotherapy. This is to be accomplished by developing models of tissue and tumor responses to repeated small doses of radiation, and by performing new experiments to test the models. The specific aims of the project are to determine the influence of dose-fractionation patterns on recovery in late-responding tissues during interfraction intervals, and on the timing and severity of acute responses; a corollary aim is to determine the potential of tumors to accelerate their regrowth in response to radiation injury. Models of acute responses will be developed and tested experimentally. Emphasis is placed on the application of applied mathematics to problems in experimental design and analysis, and to experimental tests of the mathematical models. These studies will ultimately provide the radiotherapist with guidelines for the use of accelerated fractionation and hyperfractionation, by establishing the tumor sites where they might be most beneficial and by establishing limits on the number and size of daily treatments, based on both the necessity for complete Elkind repair in late-responding tissues and the timing and severity of reactions in early responding tissues.